4-4′-Diamino-diphenylsulfone has been used for a long time in therapy as an antibacterial and in the treatment of dermatologic diseases.
In particular, it is used in clinical medicine, in association with rifampin and clofazimine, in the treatment of the leprosy.
The preparation of Dapsone is known for a long time and the synthetic methods for its preparation are interesting.
Indian Chemical Journal: 1971, 6(1), 179-181 discloses several methods. One of them, for example, teaches the preparation by a process which comprises the reaction between Na2S and p-chloronitrobenzene to obtain p-nitrothiophenol that by reaction with another equivalent of p-chloronitrobenzene forms the diamino-compound. This is acetylated by treatment with acetic acid/acetic anhydride at reflux to form the diacetylamino-compound, which is then oxidized with dichromate in glacial acetic acid. The so obtained 4,4′-diacetylaminodiphenyl sulfone is then hydrolyzed to obtain Dapsone.
Another method comprises the use of a substrate 4,4′-dinitrophenyl sulfide; the oxidation is then carried out for example with peroxides or permanganate. U.S. Pat. No. 2,385,899 discloses the oxidation of 4,4′-dinitro-diphenyl sulfide and 4,4′-diacetylaminodiphenyl-sulfide with sodium hypochloride in acetic acid at 85° C. EP 102 476 discloses the oxidation of the sulphinyl substrate to sulphone by treatment with 30% H2O2 in glacial acetic acid, as solvent, at about 100° C.
Notwithstanding several synthetic methods for preparing Dapsone have been used for a long time, it is well known that various by-products and impurities can form during its preparation and their removal requires troublesome operations, scarcely compatible with its production on industrial scale.
The object of the present invention is to provide a new synthetic process for preparing Dapsone, more suitable for its preparation on industrial scale, improving the yield and the purity, and, at the same time, also reduces the costs and is environmentally friendly.